ArticleOncotarget2016
Targeting radioresistant breast cancer cells by single agent CHK1 inhibitor via enhancing replication stress.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 33 citations in OpenAlex.
- Hypoxia Induces a Mitotic Survival Advantage After Radiotherapy in Head and Neck Cancer Cells.International journal of cancer · 2026Article
- Translational prioritization of strategies to overcome poly ADP-ribose polymerase inhibitor resistance in breast cancer based on systematic review of preclinical evidence.Discover oncology · 2026Review
- Therapy as a State-Generator: Dynamic Phenotypic Landscapes and Adaptive Stress Circuits in Chemotherapy Resistance of Breast Cancer.Antioxidants (Basel, Switzerland) · 2026Review
- Overcoming acquired doxorubicin resistance of ovarian carcinoma cells by verapamil‑mediated promotion of DNA damage‑driven cytotoxicity.International journal of oncology · 2026Article
- The Potential for Targeting GCancers · 2024Review
- The thioredoxin system determines CHK1 inhibitor sensitivity via redox-mediated regulation of ribonucleotide reductase activity.Nature communications · 2024Article
- LowTheranostics · 2024Article
- Drug Discovery Targeting Post-Translational Modifications in Response to DNA Damages Induced by Space Radiation.International journal of molecular sciences · 2023Review
- Targeting K-Ras-mediated DNA damage response in radiation oncology: Current status, challenges and future perspectives.Clinical and translational radiation oncology · 2023Review
- Chk1/2 inhibitor AZD7762 enhances the susceptibility of IDH-mutant brain cancer cells to temozolomide.Medical oncology (Northwood, London, England) · 2022Article
- New Advances in Targeted Therapy of HER2-Negative Breast Cancer.Frontiers in oncology · 2022Review
- Modulating the Radiation Response for Improved Outcomes in Breast Cancer.JCO precision oncology · 2021Review
- Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer.Gastroenterology · 2021Article
- A Genome-Wide Pooled shRNA Screen Identifies PPP2R2A as a Predictive Biomarker for the Response to ATR and CHK1 Inhibitors.Cancer research · 2020Article
- Changes in DNA Damage Repair Gene Expression and Cell Cycle Gene Expression Do Not Explain Radioresistance in Tamoxifen-Resistant Breast Cancer.Oncology research · 2020Article
- MiR-7-5p-mediated downregulation of PARP1 impacts DNA homologous recombination repair and resistance to doxorubicin in small cell lung cancer.BMC cancer · 2019Article
- Clinicopathological significance of ataxia telangiectasia-mutated (ATM) kinase and ataxia telangiectasia-mutated and Rad3-related (ATR) kinase in MYC overexpressed breast cancers.Breast cancer research and treatment · 2019Article
- Targeted Profiling of Heat Shock Proteome in Radioresistant Breast Cancer Cells.Chemical research in toxicology · 2019Article
- The clinical significance of CHEK1 in breast cancer: a high-throughput data analysis and immunohistochemical study.International journal of clinical and experimental pathology · 2019Article
- The FOXO3-FOXM1 axis: A key cancer drug target and a modulator of cancer drug resistance.Seminars in cancer biology · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 7 institutions in 2 countries.
Funding
Abstract
Radiotherapy (RT) remains a standard therapeutic modality for breast cancer patients. However, intrinsic or acquired resistance limits the efficacy of RT. Here, we demonstrate that CHK1 inhibitor AZD7762 alone significantly inhibited the growth of radioresistant breast cancer cells (RBCC). Given the critical role of ATR/CHK1 signaling in suppressing oncogene-induced replication stress (RS), we hypothesize that CHK1 inhibition leads to the specific killing for RBCC due to its abrogation in the suppression of RS induced by oncogenes. In agreement, the expression of oncogenes c-Myc/CDC25A/c-Src/H-ras/E2F1 and DNA damage response (DDR) proteins ATR/CHK1/BRCA1/CtIP were elevated in RBCC. AZD7762 exposure led to significantly higher levels of RS in RBCC, compared to the parental cells. The mechanisms by which CHK1 inhibition led to specific increase of RS in RBCC were related to the interruptions in the replication fork dynamics and the homologous recombination (HR). In summary, RBCC activate oncogenic pathways and thus depend upon mechanisms controlled by CHK1 signaling to maintain RS under control for survival. Our study provided the first example where upregulating RS by CHK1 inhibitor contributes to the specific killing of RBCC, and highlight the importance of the CHK1 as a potential target for treatment of radioresistant cancer cells.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.